rs4624606

Variant names:

• chr3-190636457-A-T
• rs4624606
• NM_002182.4:c.1051+6959A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002182.4(IL1RAP):​c.1051+6959A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 151,788 control chromosomes in the GnomAD database, including 39,273 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39273 hom., cov: 31)
• Consequence: IL1RAP NM_002182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 15 publications found

Genes affected

IL1RAP (HGNC:5995): (interleukin 1 receptor accessory protein) This gene encodes a component of the interleukin 1 receptor complex, which initiates signalling events that result in the activation of interleukin 1-responsive genes. Alternative splicing of this gene results in membrane-bound and soluble isoforms differing in their C-terminus. The ratio of soluble to membrane-bound forms increases during acute-phase induction or stress. [provided by RefSeq, Jul 2018]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002182.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	NM_002182.4	MANE Select	c.1051+6959A>T		intron	N/A	NP_002173.1	Q9NPH3-1
	IL1RAP	NM_001167931.2		c.1051+6959A>T		intron	N/A	NP_001161403.1	Q9NPH3-5
	IL1RAP	NM_001364879.1		c.1051+6959A>T		intron	N/A	NP_001351808.1	Q9NPH3-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RAP	ENST00000447382.6	TSL:1 MANE Select	c.1051+6959A>T		intron	N/A	ENSP00000390541.1	Q9NPH3-1
	IL1RAP	ENST00000317757.8	TSL:1	c.1051+6959A>T		intron	N/A	ENSP00000314807.3	Q9NPH3-5
	IL1RAP	ENST00000072516.7	TSL:1	c.1051+6959A>T		intron	N/A	ENSP00000072516.3	Q9NPH3-1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108672 AN: 151680 Hom.: 39273 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.703

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.716 AC: 108700 AN: 151788 Hom.: 39273 Cov.: 31 AF XY: 0.721 AC XY: 53545 AN XY: 74224

African (AFR) AF: 0.593 AC: 24425 AN: 41204

American (AMR) AF: 0.724 AC: 11062 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2705 AN: 3470

East Asian (EAS) AF: 0.828 AC: 4285 AN: 5176

South Asian (SAS) AF: 0.755 AC: 3644 AN: 4826

European-Finnish (FIN) AF: 0.808 AC: 8525 AN: 10552

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51764 AN: 67968

Other (OTH) AF: 0.704 AC: 1487 AN: 2112

Alfa AF: 0.740 Hom.: 5211

Bravo AF: 0.701

Asia WGS AF: 0.777 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.32
DANN	Benign	0.34
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4624606; hg19: chr3-190354246;